Radiotherapy or Surgery of the Axilla After a Positive Sentinel Node in Breast Cancer: 10-Year Results of the Randomized Controlled EORTC 10981-22023 AMAROS Trial

Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. PURPOSE The European Organisation for Research and Treatment of Cancer 10981-22023 AMAROS trial evaluated axillary lymph node dissection (ALND) versus axillary radiotherapy (ART) in patients with cT1-2, node-negative breast cancer and a positive sentinel node (SN) biopsy. At 5 years, both modalities showed excellent and comparable axillary control, with significantly less morbidity after ART. We now report the preplanned 10-year analysis of the axillary recurrence rate (ARR), overall survival (OS), and disease-free survival (DFS), and an updated 5-year analysis of morbidity and quality of life. METHODS In this open-label multicenter phase III noninferiority trial, 4,806 patients underwent SN biopsy; 1,425 were node-positive and randomly assigned to either ALND (n = 744) or ART (n = 681). RESULTS Per intention-to-treat analysis, 10-year ARR cumulative incidence was 0.93% (95% CI, 0.18 to 1.68; seven events) after ALND and 1.82% (95% CI, 0.74 to 2.94; 11 events) after ART (hazard ratio [HR], 1.71; 95% CI, 0.67 to 4.39). There were no differences in OS (HR, 1.17; 95% CI, 0.89 to 1.52) or DFS (HR, 1.19; 95% CI, 0.97 to 1.46). ALND was associated with a higher lymphedema rate in updated 5-year analyses (24.5% v 11.9%; P < .001). Quality-of-life scales did not differ by treatment through 5 years. Exploratory analysis showed a 10-year cumulative incidence of second primary cancers of 12.1% (95% CI, 9.6 to 14.9) after ART and 8.3% (95% CI, 6.3 to 10.7) after ALND. CONCLUSION This 10-year analysis confirms a low ARR after both ART and ALND with no difference in OS, DFS, and locoregional control. Considering less arm morbidity, ART is preferred over ALND for patients with SN-positive cT1-2 breast cancer.

The influence of axillary surgery and radiotherapeutic strategy on the risk of lymphedema and upper extremity dysfunction in early breast cancer patients

“…Several objective BCRL detection methods have been applied. In the AMAROS trial, an increase in arm circumference 15 cm above and below the medial epicondyle by more than 10% compared with the contralateral arm was defined as BCRL [ 3 ]. The DBCG trial (NCT02384733) also used the same measurement [ 28 ].…”

“…The new paradigm of surgery and radiotherapy has resulted in a lower complication rate. The AMAROS trial, which compared ALND with sentinel lymph node biopsy (SLNB) plus axillary radiotherapy (ART) in cN0/SLN + patients, revealed that the increase >10% in the arm circumference in the SLNB + ART group was significantly lower than that in the ALND group at 5 years (24.5% vs. 11.9%, p ＜0.001), with a low number of axillary recurrences in both groups (10-year cumulative incidence in ALND vs. ART: 0.93% vs. 1.82%, HR = 1.71) [ 3 ]. The prospective study of Naoum et al enrolled 1815 patients from 2005 to 2018, and the 5-year BCRL rates in the ALND group were significantly higher than those in the SLNB + RNI group (24.9% vs. 10.7%, p = 0.02) with comparable local control rates [ 4 ].…”

“…Nevertheless, the majority of SLN-positive patients routinely underwent ALND during the period of the above two studies, while ART was only applied when too few lymph nodes were removed or more than 3 lymph nodes were positive [ 7 ]. Since omitting ALND for breast cancer patients with a limited nodal burden has been acknowledged following the results of the Z0011 and AMAROS trials, the effect of RNI on BCRL with evolving surgical practice remains unclear [ 3 , 8 ].…”

Prediction of pathologic complete response after single-dose MR-guided partial breast irradiation in low-risk breast cancer patients: the ABLATIVE-2 trial - a study protocol

“…In patients with early-stage breast cancer, BCS followed by WBI resulted in equivalent recurrence rates and overall survival compared with mastectomy (6, 40, 41). In addition, axillary RT has replaced axillary lymph node dissection in patients with a tumor-positive sentinel node (42). Genomic tools are utilized to identify low-risk patients with no bene t from chemotherapy (43,44).…”

“This house believes that: Sentinel node biopsy alone is better than TAD after NACT for cN+ patients”

“…Subsequently, thanks to randomized studies such as IBCSG 23–01, Z0011 and Amaros, axillary dissection (AD) was abandoned also for patients with a positive sentinel node. But clinically positive axillary nodes were widely considered a contraindication to SNB in breast cancer in upfront surgery [ 2 , 4 , 5 ].…”